Demonstration of in vivo bioequivalence of a generic albuterol metered-dose inhaler to ventolin

Study objective: To use histamine bronchoprovocation and bioassay statistic al procedures to evaluate the in vivo bioequivalence of a genetic albuterol metered-dose inhaler (MDI). Design: A randomized, double-blind, balanced, crossover design was used to determine the potency of each generic albuterol MDI actuation relative to V entolin (Glaxo Wellcome; Research Triangle Park, NC) administration. One tr eatment was administered on each of 4 study days.,4 histamine bronchoprovoc ation procedure was initiated 1.25 h before and 15 min after administration of the study treatment. Patients: Twenty-four nonsmoking subjects with mild-to-moderate asthma were studied (18 to 65 years of age; FEV1, > 60% of predicted; and provocative concentration of histamine causing a 20% fall in FEV1 [PC20], less than or equal to 8 mg/mL at screening). Interventions: One and four actuations (90 and 360 mu g, respectively) of t he genetic MDI and of Ventolin MDI. Placebo inhalers were used to maintain blinding of inhaler and doses. Measurements and results: The primary outcome variable was histamine PC20 m easured after study treatment administration. A significant dose-effect rel ationship was present (p < 0.0001), Deviation from pal allelism of the gene tic and Ventolin dose-response curves (p = 0.95) and differences in overall mean response between the two formulations (p = 0.68) were not significant . Using Finney 2 x 2 bioassay statistical procedures, we estimated that one actuation of the genetic albuterol MDI was equivalent to 1.01 puffs of Ven tolin (90% confidence interval, 0.69 to 1.50). Conclusion: The genetic albuterol MDI delivers a quantity of albuterol to t he beta(2)-receptor site in the lung that is the bioequivalent to Ventolin, Further, this study reinforces the validity of this statistical methodolog y for determining iii rico bioequivalence.